Dialkyl transesterification

Sulfites. The Hterature concerning dialkyl sulfites is extensive, although less than for sulfates. Reactions involving alkylation are similar to those of sulfates. Sulfites also undergo elimination, transesterification, and isomerization. The last two parallel reactions of phosphites. 

Transesterification has become a convenient method for synthesi2ing high alkyl, aryl, or alkyl aryl carbonates. Fiber- and film-forming polycarbonates are produced by transesterifying dialkyl, dicycloalkyl, or diaryl carbonates with alkyl, cycloalkyl, or aryl dihydroxy compounds (62). 

Alkyl esters often show low reactivity for lipase-catalyzed transesterifications with alcohols. Therefore, it is difficult to obtain high molecular weight polyesters by lipase-catalyzed polycondensation of dialkyl esters with glycols. The molecular weight greatly improved by polymerization under vacuum to remove the formed alcohols, leading to a shift of equilibrium toward the product polymer the polyester with molecular weight of 2 x 10" was obtained by the lipase MM-catalyzed polymerization of sebacic acid and 1,4-butanediol in diphenyl ether or veratrole under reduced pressure. ... 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

Unactivated esters, typically alkyl esters, often show low reactivity toward lipase catalyst for transesterifications. In the case of the lipase-catalyzed polycondensation of dialkyl esters with glycols, the polymer of high molecular weight was not obtained. The molecular weight improved when vacuum conditions were used Mw reached more than 2 x 104 in the combination of diethyl sebacate and 1,4-butanediol catalyzed by lipase MM [30]. 

Dialkyl 4-pyrimidinylaminomethylenemalonates (1426, n = 2,3,5) were prepared in 70-80% yields in the base-catalyzed transesterification of diethyl 4-pyrimidinylaminomethylenemalonates (1426, n = 1) with the appropriate alkanol at ambient temperature for 120 hr in the presence of sodium hydride. Acid-catalyzed transesterification was unsuccessful (84JHC247). 

Because of the possibility of racemization during the transesterification reaction (strong basic conditions) alternative methods are reported. These include transesterification in the presence of the KF/18-crown-6 ether 461 or the use of titanium tetraalkoxides. 471 The methods are efficient and represent a route to any required dialkyl ester using diphenyl esters as starting materials. Diphenyl groups can also be removed by hydrogenation in the presence of platinum dioxide (Adams catalyst) to provide the free phosphonic acid moiety directly)46 ... 

Very often, the transesterification reaction implies the need for an alkylene or CC (e.g., EC or PC) and an alcohol in the presence of either a homogeneous or heterogeneous acidic or basic catalyst [268], to co-produce dialkyl carbonate and the alkane diol or glycol (Equation 7.30). 

Alkylene CCs have been prepared through the transesterification of appropriate glycols with dialkyl carbonates (usually diethyl or dimethyl carbonate) in the presence of a suitable catalyst. One of the first such examples was the synthesis of six-membered CCs by the transesterification of propane-1,3-diols with DEC catalyzed by sodium ethanolate (Equation 7.31) [289], The reaction was carried out at temperatures between 293 and 333 K, and a conversion yield of 40% was obtained. 

Typical protocols for the preparation of chiral allyl boronates involve Matteson homologation of vinyl boronates 159 with halomethyl lithium 160 or the vinylation of halomethyl boronate 163 with vinyl Grignard 162 followed by transesterification with dialkyl tartrate 164 (Scheme 26) <1996JOC100>. 

Another common synthesis of cyclic boron compounds involves transesterification. For example, the chiral allyl boronates 155 can be synthesized via the reaction of dioxaborolane 329 with dialkyl tartrate 330 in high yield. The transacetalization affords an attractive alternative to the formation of these chiral boronates, which are otherwise difficult to prepare (Equation 13). 

Bromo- and iodotrimethylsilane, reagents compatible with alkyne and other functionalities, are suitable for the mild P-0 dealkylation of dialkyl 1-alkynylphosphonates to give the corresponding phosphonic acids.The greater reactivity of iodotrimethylsilane will probably prove advantageous for the low-temperature dealkylation of phosphonates having triple bonds. However, transesterification of diethyl 2-propynylphosphonate with iodotrimethylsilane at -30°C followed by solvolysis with MeOH led quantitatively to the 1-propynylphosphonic icid. ... 

Although the reaction of dialkyl phosphites with orthoformic esters has been extended to triethyl trithioorthoformate," the preferred synthesis of formylphosphonate dithioacetals is usually the high-yield Michaelis-Arbuzov reaction of trivalent phosphorus compounds with the appropriate chlo-rodithioacetals.""" For the corresponding hemithioacetals, a Pummerer-type reaction of a-phos-phoryl sulfoxides with alcohols in the presence of iodine is usually the method of choice (Scheme 5.3). " ° However, hemithioacetal formation is solvent dependent and generally gives a moderate yield of product in a mixture with several other byproducts arising from transesterification reactions. 

Several reports show that it is possible to carry out a transesterification selectively at the carboxylic ester moiety of dialkyl l-(alkoxycarbonyl)methyIphosphonates rather than at the phosphonic ester moiety with primary and secondary alcohols in the presence of NaH or DMAPP For example, a number of chiral phosphonates have been prepared in high yields (80-96%) by DMAP-catalyzed transesterification of dialkyl l-(alkoxycarbonyl)methylphospho-nates with 8-phenytmenthol in toluene at reflux." " -" ... 

This method has been applied to a monomer synthesis (2.20).61 The quaternary ammonium salt is used as a phase transfer catalyst. The potassium iodide converts the starting chloride to a more reactive iodide in situ. The alcohol traps the intermediate isocyanate before it can react with the small amount of water that has to be present. If no methanol is present, the corresponding urea is formed in up to 87% yield. If only 0.3 equivalent of water is used, the product is the iso-cyanurate, the cyclic trimer of the isocyanate. Where n = 1, the isocyanatoethyl methacrylate is a useful monomer now made with phosgene (2.21).62 Dow has patented a route from ethanolamine plus a dialkyl carbonate, followed transesterification to a methacrylate carbamate, which is py-rolyzed to the isocyanate (2.22) in 50% yield.63... 

Dialkyl aminoethyl acrylic esters are readily prepared by transesterification of the corresponding dialkylaminoethanol (102,103). Catalysts include strong acids and tetraalkyl titanates for higher alkyl esters and titanates, sodium phenoxides, magnesium alkoxides, and dialkyltin oxides, as well as titanium and zirconium chelates, for the preparation of functional esters. Because of loss of catalyst activity during the reaction, incremental or continuous additions may be required to maintain an adequate reaction rate. 

Aliphatic polycarbonates (polyesters of carbonic acid) are obtained by the transesterification reaction of dialkyl carbonates (for example dimethyl carbonate) with aliphatic diols. A typical example is the polycondensation of dimethyl carbonate with 1,6 hexanediol (reaction 8.3) [4-8] ... 

Transesterification reactions between dialkyl esters of dicarboxylic acids and glycols are made using similar equipment. 

In order to obtain purer products, a process based on the transesterification of a glycol and a dialkyl or diaryl carbonates (reaction 8.33) was developed. 

When NaOMe was employed as catalyst in the initial reaction, the formation of 262 was accompanied by that of significant amounts of the 3-hydroxy-l,2-oxaphosph(V)olanes 263, again as mixtures of diastereoisomers. The latter are also obtained through the tri-ethylamine-catalysed intramolecular transesterification of the linear esters 262 Mixtures of linear and cyclic acylated phosphonic esters, e.g. the acetates of 262 and 263, result when 4-acetyloxybutan-2-one is acted upon by a dialkyl hydrogenphosphonate". ... 

In a simple synthetic example, Jung used AD-mix-P to convert 267 to 268 in quantitative yield and 93% ee, as part of study using dialkyl aminals in asymmetric induction.374 Similarly, Corey used AD-mix-a with 269 as part of synthesis of eicosanoid (11/ , 125)-oxidoarachidonic acid, [,yt the initial diol (270) was not isolated. Internal transesterification led to the hydroxy-lactone 271 in 70% yield and 88% ee. After crystallization, 271 was obtained in 86% yield and 94% ee after crystallization. A comparison of 268 and 271 shows that the different catalysts have produced diols with the opposite absolute configuration. 

The latter have been prepared in high yields by the transesterification of the cmde dialkyl arylboronates in refluxing two-phase ethyleneglycol / toluene mixture [147]. 

The synthesis of higher dialkyl H-phosphonate homologues usually includes the initial treatment of phosphoms trichloride with methyl alcohol, and then the transesterification of so-formed dimethyl H-phosphonate with higher alcohols [16,17],... 

It has been assumed that in the noncatalyzed transesterification of dialkyl H-phos-phonates, these compounds react with their four-coordinated phosphonate form [28,29], AMI semiempirical calculations [30] of the model transesterification of dimethyl H-phosphonate with methanol indicate that in the first stage of this reaction, dimethyl H-phosphonate and the nucleophile form a pentacoordinated intermediate n via a four-centered cyclic transition structure I. The trigonal-bipyramidal intermediate n undergoes pseudorotation [17c,31] and via a new transition structure in of the same type as I, forms the monotransesterificated product. The rate of transesterification depends both on the type of substituents at phosphorus and the nucleophiUcity of the corresponding alcohol. 

It is suggested that when the transesterification reaction is carried out in the presence of a basic catalyst, dialkyl H-phosphonates react via their tricoordinated phosphite tautomeric form [32,35], The first step of the reaction is tautomerization of phosphonate form into phosphite. 

The transesterification of dialkyl H-phosphonates with hydroxyl-containing compounds is accompanied by side reactions, resulting in the formation of ether compounds and H-phos-phonic acid monoalkyl esters [28,36,37]. The formation of these side products is due to the nucleophilic attack of the oxygen atom of the alcohol on the ot-carbon atom of the alkoxy group, the second electrophilic center in the molecule of dialkyl H-phosphonates. 

Dialkyl alkylene diphosphonates obtained by transesterification of dialkyl H-phosphonates with diols in the excess of H-phosphonate diesters are bifunctional monomers possessing two reactive P-H groups. The addition of ketones or aldehydes to dialkyl alkylene diphosphonates resulted in the formation of the corresponding bis(a-hydroxyalkylphosphonate)s [185]. 

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